gene therapy, chemotherapy, and peripheral stem cell transplantation in treating patients with hiv-related non-hodgkin's lymphoma

Conditions: Lymphoma

Summary: rationale: inserting the gene for revm10 into a person's peripheral stem cells may improve the body's ability to fight cancer or make the cancer more sensitive to chemotherapy. purpose: phase i/ii trial to study the effectiveness of revm10-treated stem cells plus chemotherapy and peripheral stem cell transplantation in treating patients who have hiv-related non-hodgkin's lymphoma.

objectives: i. determine the safety of infusion of revm10 or revm10/polas transduced hematopoietic stem cells (hsc) in addition to high dose chemotherapy and standard peripheral blood stem cell support in patients with hiv-1 related non-hodgkin's lymphoma. ii. determine gene marking of lymphocytes and myeloid cells in peripheral blood, bone marrow, and/or lymph nodes after infusion of revm10-hsc or revm10/polas-hsc in these patients. iii. determine the antiretroviral effect of this treatment in these patients. outline: this is a multicenter study. patients receive mobilization therapy and undergo leukapheresis according to a standard protocol. high dose chemotherapy is administered on days -7 to -1, also according to a standard protocol. on day 0, autologous hematopoietic stem cells transduced with genes revm10 or revm10/polas are infused. unmodified autologous peripheral blood stem cells are reinfused on day 1. patients are followed daily for 2 weeks, weekly for 2 weeks, monthly for 1 year, then annually thereafter. projected accrual: approximately 15 patients will be accrued for this study within 14 months.

Eligibility criteria:
disease characteristics: hiv-1 infection documented by elisa and western blot histologically proven non-hodgkin's lymphoma showing at least partial response to standard chemotherapy regimen poor prognosis in first chemotherapy induced remission increased ldh and/or stage iii or iv and/or reduced performance status (ecog 2 or worse) or response but no complete remission following four courses of standard chemotherapy or responding relapse after primary therapy no primary cns lymphoma no uncontrolled meningeal lymphoma at mobilization patient characteristics: age: 18 and over performance status: see disease characteristics life expectancy: not specified hematopoietic: absolute neutrophil count at least 1500/mm3 platelet count at least 100,000/mm3 cd4 count at least 100/mm3 hepatic: bilirubin less than 2 mg/dl (unless taking indinavir) sgot and sgpt less than 2 times normal no hepatitis renal: creatinine less than 2.0 mg/dl pulmonary: dlco greater than 60% other: not pregnant or nursing fertile patients must use effective contraception no active mycobacterium avium-intracellulare infection or cmv disease no cerebral toxoplasmosis or cryptococcal meningitis at least 6 months since prior alcohol or substance abuse at least 1 year since cns disease or seizures no other medical condition that would preclude study prior concurrent therapy: biologic therapy: not specified chemotherapy: see disease characteristics no concurrent chemotherapy for kaposi's sarcoma endocrine therapy: not specified radiotherapy: not specified surgery: not specified other: at least 30 days since prior treatment for serious opportunistic infections

Keywords: aids-related peripheral/systemic lymphoma aids-related diffuse large cell lymphoma aids-related immunoblastic large cell lymphoma aids-related small noncleaved cell lymphoma aids-related diffuse mixed cell lymphoma aids-related diffuse small cleaved cell lymphoma aids-related lymphoblastic lymphoma